What is the current role
of the oral glucose tolerance test (OGTT)
in the diagnosis and management
of diabetes mellitus?

Response from William E. Winter, MD, Desmond Schatz, MD, 01/17/2003
The OGTT can play an important role in the diagnosis of diabetes as well as screening for abnormal glucose levels (ie, prediabetes or diabetes). However, the OGTT has no role in the management of diabetes.

According to the American Diabetes Association (ADA) recommendations, [1] in the absence of ketoacidosis or nonketotic hyperglycemic coma, hyperglycemia must be documented on 2 separate occasions to diagnose diabetes. Hyperglycemia is diagnosed using any 1 of the following 3 criteria: (1) elevated fasting plasma glucose greater than 7 mmol/L (126 mg/dL); (2) elevated 2-hour plasma glucose during an OGTT greater than 11 mmol/L (200 mg/dL); or (3) a random plasma glucose greater than 11 mmol/L (200 mg/dL) in a symptomatic individual. Any combination of tests for hyperglycemia can be used as long as hyperglycemia is documented on 2 different days. If a patient is undergoing an OGTT and the fasting plasma glucose is found to be grteater than 7 mmol/L (126 mg/dL), there is no additional diagnostic information gained if the 2-hour plasma glucose is greater than 11 mmol/L ( 200 mg/dL). It can be argued that if the fasting plasma glucose is found to be elevated, the OGTT should not be completed.

A reasonable approach for diagnosing diabetes in symptomatic subjects is to first obtain a random plasma glucose. If this is elevated (ie, ≥ 11 mmol/L or 200 mg/dL), the patient should be asked to return the next day for measurement of a fasting plasma glucose. If this value is ≥ 7mmol/L or 126 mg/dL, the diagnosis of diabetes is established because the criteria for hyperglycemia on 2 occasions has been met. If the fasting plasma glucose is < 7 mmol/L or 126 mg/dL, the 75-g glucose challenge for the OGTT should be administered and the 2-hour plasma glucose measured. If this is ≥ 7 mmol/L or 200 mg/dL, the diagnosis of diabetes is established because the criteria for hyperglycemia on 2 occasions has now been met.

Using the 1997 ADA guidelines, the OGTT is relatively simple to perform. To be tested, subjects must be on a stable diet, at a stable weight, with a stable level of exercise, and without acute illness or recent hospitalization. Carbohydrate (100-150 g/day) is taken as part of the diet for 3 days prior to the scheduled OGTT. The subject is to fast overnight, usually for 8-14 hours, and should take nothing by mouth except water. No medications, caffeine, or tobacco are to be taken until the completion of the test. Two samples are drawn: time zero and 2-hour samples. Thus the OGTT can be termed a "2 + 2" (2 samples - 2 hours). Time zero is when the subject begins to drink the sugar beverage. Adults receive 75 g of glucose, whereas children receive 1.75 g per kg of weight to a maximum of 75 g. The beverage should be consumed in 5 minutes or less. The maximum glucose concentration in the beverage is 25 g per 100 mL.

Prediabetes is diagnosed when the fasting plasma glucose is between 6.1 mmol/L (110 mg/dL) and 7.0 mmol/L (125 mg/dL) (ie, impaired fasting glucose) and/or the 2-hour plasma glucose on the OGTT is between 7.8 mmol/L and 11 mmol/L (140 mg/dL and 199 mg/dL) (ie, impaired glucose tolerance) in the absence of hyperglycemia as defined above. Individuals with prediabetes are at high risk to progress to frank type 2 diabetes unless the patient loses weight, exercises, and/or alters diet. Recent studies have conclusively shown that diet and exercise intervention in prediabetes reduces the progression to type 2 diabetes by 58%.[2] These nonpharmacologic interventions are more successful than metformin alone, which achieved a 31% reduction in progression to type 2 diabetes.[2]

The ADA has provided guidelines for screening for diabetes[3] and prediabetes[4] in adults. While fasting plasma glucose is the recommended screening tool, the ADA stated in 2001 that the OGTT is an acceptable alternative. The ADA recommends that physicians consider screening all adults age 45 or older every 3 years for abnormal glucose levels. When an individual is obese, has a family history of diabetes, has hypoalphalipoproteinemia, hypertriglyceridemia, or hypertension, has impaired fasting glucose or impaired glucose tolerance, is from an ethnic minority (ie, African American, Hispanic American, Native American, or Asian American/Pacific Islander), or is a woman who had gestational diabetes or delivered an infant who weighed more than 9 lb, screening should begin before age 45. The American Association of Clinical Endocrinologists recommends that screening begin as early as age 30. There are extensive data showing that the OGTT is more sensitive than measuring fasting plasma glucose alone for the diagnosis of diabetes or prediabetes.

The last use of the OGTT is in screening for diabetes during pregnancy (ie, gestational diabetes mellitus).[5] Physicians can elect to screen with a modified OGTT (1 hour after 50-g glucose challenge, fasting or nonfasting; normal response < 7.8 mmol/L (140 mg/dL) or perform a 3-hour OGTT (100-g glucose challenge, blood drawn at times: 0, +1, +2, and +3 hours). If the 1-hour screen is normal, the 3-hour OGTT is not required. If the screen is positive, the 3-hour OGTT must be performed. In pregnancy, in the absence of criteria that meet the traditional diagnosis of diabetes, diabetes is diagnosed when 2 or more values meet or exceed the following cut points: fasting: 5.3 mmol/L (95 mg/dL); 1 hour: 10 mmol/L (180 mg/dL); 2 hours: 8.6 mmol/L (155 mg/dL); and 3 hours: 7.8 mmol/L (140 mg/dL). The ADA also recommends that if the woman is at low risk for gestational diabetes, her physician can elect not to screen for gestational diabetes. However, the American College of Obstetrics and Gynecology does not accept this recommendation. The ADA definition of low risk is: age < 25 years; normal body weight; no family history of diabetes; and ethnicity other than African American, Hispanic American, or Native American. As an alternative to the 3-hour OGTT, 75 g of glucose can be administered with time points drawn at 0, 1, and 2 hours with the respective cut points being 5.3 mmol/L (95 mg/dL), 10 mmol/L (180 mg/dL), and 8.6 mmol/L (155 mg/dL). Gestational diabetes is diagnosed when 2 or more thresholds are met or exceeded. However, in comparison with the 3-hour, 100-g test, there are fewer data on the performance of the 2-hour, 75-g test in pregnancy.

In summary, the OGTT can play an important role in both the diagnosis of diabetes and the screening for diabetes and prediabetes. While the OGTT is less reproducible than fasting plasma glucose values, it is more sensitive for the detection of prediabetes or diabetes.